Hepatitis C virus; its implication for endodontists.

Over 170 million patients worldwide are chronically infected with Hepatitis C virus (HCV); making it a globally important infection. Dentists constantly handle sharp instruments infected with biological fluids and are therefore considered at high-risk of contracting HCV infection. Needle-stick injuries seem to be the most common route of exposure to blood-borne pathogens in dental practice. Moreover, endodontist's constant use of sharp instruments such as endodontic files with limited operative vision in a small working field (i.e. root canal system) increases their risk of exposure to infection. The aim of this study was to review the epidemiology of HCV infection in dental healthcare staff and the tests required for its diagnosis. We also look at the protocols for dental treatment in infected individuals and screening and dental examination tailored for HCV patients.


Introduction
epatitis C virus (HCV), also known as parentally transmitted or post transfusion non-A non-B hepatitis, was first identified in 1989. It is a single-stranded positive-sense RNA virus, enclosed in an envelope with a diameter of ~50 nm and is classified in a separate genus of Hepacivirus as the third member of the Flaviviridae family (the other two genera remain as Pestivirus and Flavivirus) [1,2].
With more than 3% of world's population being chronically infected (170 million individuals) in two decades, HCV infection is now considered a globally significant disease [2,3]. The prevalence of HCV infection is estimated to be higher than human immunodeficiency virus (HIV) or even hepatitis B virus (HBV), in the USA. Infection with HCV is the most leading cause of liver transplantation worldwide. The most important route of transmission before 1989 was blood transfusion [4][5][6]. Mortality rate of HCV chronic infection is increasing in many parts of the world [5]. The prevalence of HCV infection is estimated to be 0.16% in Iran [7].
Six major genotypes (namely 1 to 6) of HCV with different geographically distribution have been identified so far. Genotypes 1, 2 and 3 are distributed worldwide with genotype 1 accounting for 40-80% of all infected cases. Genotype 4 is generally found in the Middle East and Egypt, genotype 5 in South Africa and genotype 6 in South-East Asia [1,8].
To date no HCV-effective vaccine has been developed. In addition, treatments are focused upon achieving a sustained virological response with a combination of interferon and ribavirin, which are usually accompanied with some side effects [9][10][11].
The routes of disease transmission include intravenous drug abuse, non-protected sexual contact with multiple partners, iatrogenic acquisition (e.g. haemodialysis), accidental exposure such as needle-stick injuries (NSI) and vertical transmission from mother to the infant. However, in 30-40% cases of HCV infection, the route of acquisition cannot be identified [12,13]. The results of a recently published paper showed that although weak, there is an undoubted risk of HCV transmission and cross contamination in dental care environment, and during dental treatments especially when precautionary methods fail [14].
In recent years, more attention has been dedicated to educate undergraduate and postgraduate dental students to H The seroprevalence of anti-HCV among dentists was low.
No occupational exposure conditions were associated to the seroprevalence of HCV.

Brazil, 2006 [16]
Dentists working in a town in the state of Sao Paulo in Brazil Serum anti-HCV; confirmed by PCR 135 (0.7%) The study alerts using standard precautions during professional dental practice to avoid occupational acquisition of HBV and HCV.

Israel, 2009 [17]
Dentists attending an annual dental conference Serum anti-HCV 296 (0.33%) The study did not mention HCV as a hazard to dental professionals. However, infection control guidelines should be strictly followed.

Germany, 2000 [19]
215 dentists and 108 dental assistants attending the 1997 annual meeting of the Berliner Zahnärztekammer Serum anti-HCV 323 (0.3%) These results suggest that occupational transmission of HCV in dental settings occurs sometimes, but not frequently. Infection with HBV is 25 times higher.
enhance their knowledge on prevention of blood-borne infections (BBI). The results of recent studies on dental students' knowledge on blood-borne pathogens show that the level of students' knowledge about infectious diseases and their routes of transmission, increases as they enter higher academic semesters [20,21]. Moreover, senior students showed a more positive approach and less discriminating attitudes toward patients with BBI in comparison with junior students. It seems that using these programs prepares the future dentists for their up-coming challenges when managing patients with BBI. In addition, periodic mandatory attendance of dental health care workers (DHCW) in continuing education programs will keep them upto-date regarding this issue. Although different aspects of HIV infection has been studied in dentistry, there is rather low information regarding HCV infection in dental practice [22]. Most of the reports have been performed on different groups of DHCWs with variable subjects and methodology. Therefore, the aim of this study is to review the implications of HCV in endodontic practice; including the precautionary methods and universal cross-infection control protocols during daily practice as well as post-exposure strategies.

HCV infection in DHCWs
Dentists can be exposed to biological fluids through skin and mucous membranes or through percutaneous injuries, with the latter being the most common route of exposure. Blood exposure incidents, which may cause the transmission of blood-borne viruses, occur regularly during dental treatment procedures due to the close proximity to patient tissues, sharp instruments such as endodontic files, limited visual field in a small working area as well as the frequent patient movements during endodontic practice [23][24][25]. The risk of being infected with HCV after a single needle-stick injury is 3% [15,20]. Using the anesthetic syringe and incorrect needle recapping procedures holding the cap with one hand and re-sheathing the needle with the other, are shown to be the most important causes of NSI in dentists and dental hygienists [26]. The risk of HCV infection following a blood splash is unknown but is believed to be greater if the source patient is positive for HCV-RNA and does not occur if patient is HCV-RNA negative [27].
The results of a nationwide study in the Netherlands showed that blood exposure incidents occur frequently in dental settings, irrespective of the type of practice. Because of such accidents, dental clinics need to have a protocol for handling blood exposure incidents according to safe working practice guidelines [23]. There are few reports on epidemiology of HCV infection in DHCWs [16,17,19]. According to our search results, no previous report has been performed particularly on endodontists. Although the World Health Organization (WHO) states that dentists are at greater risk of HCV infection, there are studies showing that the prevalence of HCV infection in this group is similar or even lower than that of the general population [15][16][17][18][19]. The prevalence of HCV infection in DHCWs is shown in Table 1. Previous papers demonstrated that the possibility of acquiring HCV infection is commonly related to age and work experience [16]. Also, a study performed in Brazil showed that anti-HCV seropositivity in DHCWs is significantly associated with a history of blood transfusion and a serologic test of HCV [15].
According to the results of the available reports, HCV infection in dentists is similar or lower than that of the general population. However, due to the importance of probable transmission of HCV in dental practice, the issue is more significant. Using standard precautionary methods prevent both dentists and their patients from being infected.

Serologic tests
Most HCV-infected patients (60 to 70%) are asymptomatic. When symptoms do occur, they are nonspecific including fatigue, nausea, anorexia, myalgia, arthralgia, weakness, and weight loss [28]. It has been demonstrated that patients' medical histories are unreliable in identifying the exposure to blood-borne pathogens [29]. Dentists should be aware of HCV diagnostic tests which patients might be referred with. Although corresponding data shows that body fluids such as saliva and urine contain viral particles, routine diagnostic tests are still performed on serum samples [5,30].
HCV diagnostic tests include the HCV antibody enzyme immunoassay (EIA), different generations of recombinant immunoblot assay (RIBA-1, 2 or 3) and quantitative HCV RNA-polymerase chain reaction (PCR). The most widely used initial assay for detecting HCV antibodies is the EIA. Quantitative viral load tests measure the amount of virus in blood. Quantitative studies provide information on initial viral load, viral load reduction with therapy and a sustained virologic response, defined as undetectable HCV by PCR, six months after ceasing the therapy. However, levels of HCV-RNA do not correlate directly with liver injury, duration of infection or disease severity. Table 2 explains the results and interpretation of HCV diagnostic tests. To analyze the liver function, patients might undergo some blood tests for assessment of liver enzymes as well as liver biopsy [28,[31][32][33].
Detection and quantification of HCV-RNA is useful in order to: i) diagnose a chronic HCV infection; ii) identify patients who need antiviral therapy; iii) monitor the virological responses to antiviral therapy; and iv) identify amino acid substitutions responsible for resistance to specific inhibitors of HCV viral proteins [33].
Recently the application of oral fluid for the detection and diagnosis of HCV infection has been evaluated repeatedly. Although most studies demonstrated that oral fluids [saliva and more specifically the gingival crevicular fluid (GCF)] can be used in HCV diagnosis, the appropriate measuring tool with reliable specificity is not available yet. More studies are recommended to design appropriate tests and validate tools [5].

Dental treatment for HCV-infected patients
Living with HCV, comes along with an array of potentially serious consequences. Apart from physical/medical issues, social stigma is also an issue that viral hepatitis patients might face [22].
National and international guidelines such as the needle-stick safety act in 2001, were developed to help minimizing the risk of exposure to blood-borne pathogens in DHCWs including dental personnel [26]. While dentists and non-infected patients can be infected with hepatitis following inadequate sterilization and other precautionary methods, adequate measures should definitely be taken [34].
One of the most significant phenomena associated with hepatitis infected patients is DHCWs' fear of treating them. HCVinfected patients have significant oral health needs [35]. Unfortunately, the results of previous studies showed that a number of DHCWs prefer not to treat patients affected with HCV. Such a behavior is not only unethical but also induces patients to conceal parts of their medical history which will be detrimental for both patient and health care worker.
The results of a study aiming at evaluating DHCWs attitudes toward caring for people with HCV performed in Japan showed that significant associations exist among DHCW's knowledge about HCV and their self-reported behavior towards this population. Thirty percent of dentists indicated that patients with HCV should be given the last appointment of the day. Dentists, who reported that they complied with infection control guidelines, were significantly more likely to treat people with HCV. Additionally, 14% of dentists stated that they did not want to treat injecting drug users [36]. The results of a study performed in Australia showed that all dentists perform dental treatment on the patients with HCV even without changing their personal protective methods [22].
Dentists should keep in mind that the best patients are those who inform us about their blood contamination. If we want them to inform us of the issue, our behavior should be non-discriminative and understanding. Our practice should be the same for all patients as they may carry a blood-borne virus unknown to us and/or themselves.

Dental check-ups for HCV infected patients
Previous reports showed that infection with HCV might accompany a number of extrahepatic conditions. Mixed cryoglobulinemia, glomerulonephritis, polyarteritis nodosa, rashes, renal disease, neuropathy and lymphoma are strongly associated with HCV infection. In addition, some oral conditions have been found to be related to HCV [37,38].
There are just few reports on oral health of HCV infected patients, mostly performed in developed countries. The results of all these investigations show serious oral health needs in this group of patients [39,40]. There are also oral mucosa conditions related to HCV infection. Reports show that oral lichen planus (OLP) is also associated with virus infection in some parts of the world [41,42]. Replication of viral particles in salivary glands as well as antiviral therapies might cause symptoms similar to Sjogren's syndrome and hyposalivation [43]. Besides, other conditions related to HCV infection such as oral cancer and pemphigus need to be assessed more precisely.
Dental problems might delay the administration of HCV treatments. Plus, dental problems might worsen after applying antiviral treatments because of their side effects [44]. Patients with HCV infection should be routinely screened for oral health problems. Dentists should also be aware of probable and common conditions in the oral mucosa in this population and should meticulously assess their patients.

Conclusion
HCV infection is a condition with global impact. Along with common routes of transmission, DHCWs are always suspected whether to infect their patients or get infected. Although there are reports informing that dentists and oral surgeons have infected their patients with HBV during dental treatments, to date there is no similar report on HCV. However, available reports imply such threat in dentistry if universal infection control strategies are not adhered to. Further studies are also needed to assess the prevalence of HCV among DHCWs.